Project Summary/Abstract Drug addiction is a massive public health concern that inflicts extensive burdens on our economy and society. The harmful consequences of drug abuse extend far beyond the addicts and gravely impact their families. A growing body of evidence suggests that the children of fathers who consumed drugs around the time of conception show altered brain function and behavioral abnormalities. Using a highly translational paradigm of paternal opioid drug taking, this projects aims to identify biomarkers and mechanisms predictive of addiction susceptibility. The focus of the proposed studies will be changes in gene expression and behavior produced by paternal opioid exposure that emerge during adolescence in first generation progeny and are predictive of higher addiction-like traits in adulthood. This multifaceted project will combine behavioral and molecular biological approaches to identify functionally relevant mechanisms during puberty that confer a higher propensity to develop addiction later in life. Overall, this research will establish a strategy to delineate functional mechanisms associated with addiction susceptibility and develop a platform to study how environmental insults can shape and affect the likelihood of individuals to develop psychiatric diseases.